The Chemical Library Screening Shared Resource (CLS) offers Cancer Center scientists the ability to develop and conduct large-scale chemical library screens for the generation of selective probes of biochemical processes of tumor biology and for the discovery of compounds that can be developed further as drug leads for therapeutic applications. High-throughput screening is not widely available at academic institutions; thus, this resource provides our Cancer Center with rare access to technology, expertise and infrastructure resources that will enable them to develop novel means for characterizing cellular targets involved in tumor pathogenesis and tumor onset that will advance the development of new lead molecules for anti-tumor therapies. The CLS consists of 4 specialized but highly integrated facilities: 1) the High Throughput Assay Development Facility supports the development, miniaturization, optimization, and validation of biochemical and cell-based high throughput assays, as well as supports follow-up analysis of screens, including IC50 determination, structure-activity-relationship (SAR) and mechanism-of-action studies; 2) the Compound Management and HT Screening Facility, that curates the Institute's compound collections and performs the large-scale automated screening; 3) the High Content Screening (HCS) Facility that supports imagebased high content assays utilizing high throughput microscopy, as well as automated microscopy for nonscreening applications - This facility also supports the image-based screening efforts of the Functional Genomics Shared Resource; and 4) the Medicinal Chemistry Facility provides both technical and scientific assistance in medicinal chemistry, synthesis, structure-activity relationship development, and generates optimized compounds for preclinical studies. CLS supported over half (34) of the Cancer Center laboratories in the last year. Chemical genomics has become a major focus of the Burnham Cancer Center, and has many opportunities for providing insight into potential therapeutic targets and strategies. CCSG funding of CLS leverages a substantial Institutional and NIH MLPCN investment in the Center for Chemical Genomics infrastructure, and is critical to bringing this cutting edge technology to Cancer Center researchers by funding facility personnel that conduct their projects. Overall, $189,798 in CCSG support is requested in the first year, representing 10.5% of the total projected annual CLS Shared Resource operating budget.